This project intends to continue the investigation of the protein-protein interactions which cause sickle cell anemia. The technique of quasi-elastic light scattering will be used to study the aggregation of hemoglobin S molecules. Quasi-elastic light scattering provides an unusually sensitive method for detecting the initial aggregation of deoxyhemoglobin S molecules and for determining the distribution of particle sizes. This aggregation gives rise to the fibers which distort the erythrocytes in sickle cell anemia, thus study of the initial steps will clarify the mechanism of formation of the fibers. As an auxilary technique, electron microscopy will be used to establish the size of the aggregates of deoxyhemoglobin S. By comparison of the results of electron microscopy with those of light scattering, it may be possible to get a complete picture of the kinetics and molecular weight distributions which occur during the polymerization of deoxyhemoglobin S. From such data, information about the molecular mechanism of sickle cell hemoglobin aggregation can be obtained. For example, the enthalpy of aggregation, the degree of cooperativity of aggregation, and the mechanism of aggregation may be determined. Quasi-elastic light scattering will also be used to determine the dependence of aggregation of hemoglobin S on oxygen concentration, hemoglobin S concentration, pH, salt concentration, amount of 2,3 diphosphoglycerate bound, and the presence of other forms of hemoglobin.